EP1649864B1 - Therapeutische und/oder präventive zusammsentzung für periodontale erkrankungen - Google Patents

Therapeutische und/oder präventive zusammsentzung für periodontale erkrankungen Download PDF

Info

Publication number
EP1649864B1
EP1649864B1 EP04771237A EP04771237A EP1649864B1 EP 1649864 B1 EP1649864 B1 EP 1649864B1 EP 04771237 A EP04771237 A EP 04771237A EP 04771237 A EP04771237 A EP 04771237A EP 1649864 B1 EP1649864 B1 EP 1649864B1
Authority
EP
European Patent Office
Prior art keywords
composition
acid
periodontal disease
sasa
mass
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Fee Related
Application number
EP04771237A
Other languages
English (en)
French (fr)
Japanese (ja)
Other versions
EP1649864A4 (de
EP1649864A1 (de
Inventor
Yuuzou Tsuchida
Mitsuo; c/o Hououdou Co. Ltd. KAWABE
Kunitomo Watanabe
Kotarou Tsuchida
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Hououdou Co Ltd
Original Assignee
Hououdou Co Ltd
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Hououdou Co Ltd filed Critical Hououdou Co Ltd
Publication of EP1649864A1 publication Critical patent/EP1649864A1/de
Publication of EP1649864A4 publication Critical patent/EP1649864A4/de
Application granted granted Critical
Publication of EP1649864B1 publication Critical patent/EP1649864B1/de
Anticipated expiration legal-status Critical
Expired - Fee Related legal-status Critical Current

Links

Images

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/361—Carboxylic acids having more than seven carbon atoms in an unbroken chain; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/88—Liliopsida (monocotyledons)
    • A61K36/899—Poaceae or Gramineae (Grass family), e.g. bamboo, corn or sugar cane
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/12—Carboxylic acids; Salts or anhydrides thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/30—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds
    • A61K8/33—Cosmetics or similar toiletry preparations characterised by the composition containing organic compounds containing oxygen
    • A61K8/36—Carboxylic acids; Salts or anhydrides thereof
    • A61K8/365—Hydroxycarboxylic acids; Ketocarboxylic acids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9789—Magnoliopsida [dicotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K8/00—Cosmetics or similar toiletry preparations
    • A61K8/18—Cosmetics or similar toiletry preparations characterised by the composition
    • A61K8/96—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution
    • A61K8/97—Cosmetics or similar toiletry preparations characterised by the composition containing materials, or derivatives thereof of undetermined constitution from algae, fungi, lichens or plants; from derivatives thereof
    • A61K8/9783—Angiosperms [Magnoliophyta]
    • A61K8/9794—Liliopsida [monocotyledons]
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P1/00—Drugs for disorders of the alimentary tract or the digestive system
    • A61P1/02—Stomatological preparations, e.g. drugs for caries, aphtae, periodontitis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/10—Antimycotics
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61Q—SPECIFIC USE OF COSMETICS OR SIMILAR TOILETRY PREPARATIONS
    • A61Q11/00—Preparations for care of the teeth, of the oral cavity or of dentures; Dentifrices, e.g. toothpastes; Mouth rinses

Definitions

  • the present invention relates to a composition for use in treating and/or preventing the periodontal disease, which comprises an extract originated from the plant: Sasa (bamboo grass).
  • Streptococcus mutans is closely involved in the decayed teeth or caries.
  • periodontosis is related to the abnormal proliferation of periodontal disease-related microorganisms within periodontal pockets.
  • known examples of such periodontal disease-related microorganisms include Actinobacillus actinomycetemcomitans, Porphyromonas gingivalis, Bacteroides forthythus, Prevotella intermedia, Fusobacterium nucleatum, Capnocytophaga spp., corroding organisms (Wolinella spp., Campylobacter gracilis, and Eikenella corrodens), Eubacterium spp., and Treponema spp.
  • the initial.two kinds of or the first and second microorganisms (Actinobacillus actinomycetemcomitans and Porphyromonas gingivalis) have been regarded as important in the disease.
  • Candida albicans has been known as a causal bacterium for the "thrush (candidal stomatitis)" and there have recently been proposed some opinions which point out the close correlation between the abnormal proliferation of Candida spp. within the oral cavity and the periodontosis.
  • the extract from Sasa albo-marginata has an antimicrobial activity.
  • antimicrobial activities as those against Staphylococcus aureus, Pseudomonas aeruginosa and Escherichia coli, which are known as causal bacteria for infectious diseases of wound and those against Helicobacter pylori known as a causal bacteria for the gastric ulcer.
  • the Sasa extract has the antimicrobial activity effective for any kind of bacteria and it has not likewise generally been known that an extract derived from a natural source, which shows an antimicrobial activity against bacteria, also shows an antimicrobial activity against fungi such as Candida spp.
  • JP-A-2001151655 describes a dentrifice for preventing periodontitis, comprising a Sasa veitchii extract.
  • the present invention provides a composition for use in treating and/or preventing the periodontal disease, which comprises an extract originated from the plant: Sasa (bamboo grass) (hereafter referred to as "Sasa extract”).
  • the present invention more specifically provides a composition for use in treating and/or preventing the periodontal disease, which comprises the Sasa extract and an organic acid.
  • composition for use in treating and/or preventing the periodontal disease according to the present invention is preferably in the form of a cream.
  • the term "periodontal disease” used is defined so as to include not only the “periodontosis” which has been said to be related to the abnormal proliferation of periodontal disease-related microorganisms, but also the “decayed teeth” in which Streptococcus mutans is closely involved. Accordingly, the composition for use in the prevention and/or treatment of the periodontal disease according to the present invention likewise includes a composition for use in treating and/or preventing the "periodontosis" as well as the "decayed teeth”.
  • the inventors of this invention have variously investigated the antimicrobial activities of the Sasa extract against a variety of bacteria, have found that if the Sasa extract is used in a concentration (as expressed in terms of the solid content) ranging from 1 to 50% by mass, preferably 2 to 25% by mass and more preferably 4 to 15% by mass, it can show conspicuous antimicrobial activities against periodontal disease-related microorganisms (such as Actinobacillus actinomycetem-comitans, Porphyromonas gingivalis, Bacteroides forthythus, Prevotella intermedia, Fusobacterium nucleatum, Capnocytophaga spp., corroding organisms (Wolinella spp., Campylobacter gracilis, and Eikenella corrodens), Eubacterium spp.
  • periodontal disease-related microorganisms such as Actinobacillus actinomycetem-comitans, Porphyromonas gingivalis
  • the antimicrobial activity of the Sasa extract can be improved by the incorporation of an organic acid such as malic acid into the same and have thus completed the present invention.
  • the solid content of the Sasa extract is less than 1% by mass, the resulting product would show only a limited effect of treating and/or preventing the periodontal disease, while the use thereof in a concentration of higher than 50% by mass is not preferred because of its extremely high stimulation.
  • Sasa (bamboo grass) used as a raw material for the Sasa extract which is the effective component of the composition for use in treating and/or preventing the periodontal disease according to the present invention is not restricted to any specific one and all of the plants belonging to Sasa Makino et Shibata.
  • Sasa paniculata Makino et Shibata examples thereof include Sasa paniculata Makino et Shibata, Sasa albo-marginata, Sasa kurilensis Makino et Shibata, OKUYAMA Sasa, EZOMIYAMA Sasa, Sasa palmate Nakai, YAHIKO Sasa, Sasa megalophylla Makino et Uchida, MIYAMA Sasa, SENDAI Sasa, YUKAWA Sasa, ABOI Sasa and ONUKA Sasa.
  • Sasa paniculata Makino et Shibata and Sasa albo-marginata CHUGOKU Sasa and HTDA Sasa
  • the Sasa extract used in the present invention is preferably one prepared by extracting raw leaves or dried leaves of a Sasa plant, preferably dried leaves thereof with water maintained at a temperature ranging from 100 to 180°C at ordinary pressure or while applying a pressure.
  • the extraction method is not restricted to any particular one, but usable herein includes, for instance, that disclosed in Japanese Patent No. 3,212,278 (Japanese Un-Examined Patent Publication Hei 11-196818 ). More specifically, leaves of a Sasa plant are extracted at a temperature ranging from 100 to 180°C for 5 to 30 minutes using a pressurized hot water extraction device, the resulting extract is separated from a moisture-containing solid content (moisture content: 40 to 70%) in a moisture separator, thereafter the moisture-containing solid content is treated at a temperature ranging from 100 to 200°C for 5 to 60 minutes in a saturated vapor-heating device, the solid content thus treated is again treated at 100 to 180°C for 5 to 30 minutes using a pressurized hot water extraction device to give an extract and the extracts obtained in the first and second extraction steps are combined prior to practical use.
  • Examples of commercially available Sasa extracts each comprising 50% by mass of the Sasa extract as expressed in terms of the solid content include “TWEBS” manufactured and sold by Hououdou Co., Ltd. and “AHSS” manufactured and sold by Chloroland Moshiri Co., Ltd.
  • the Sasa extract thus obtained contains sulfur atom-containing components and the content thereof as expressed in terms of the amount of sulfur atom ranges from about 4 to 10 mg and usually about 6 to 9 mg per one gram of the solid content of the Sasa extract. Principal constituents of the sulfur atom-containing components are considered to be sulfur atom-containing amino acids.
  • composition for use in treating and/or preventing periodontal disease comprises such sulfur atom-containing components derived from the Sasa extract in an amount preferably ranging from 4 to 500 mg, more preferably 8 to 250 mg and most preferably 16 to 150 mg per 100 g of the composition as expressed in terms of the amount of sulfur.
  • the Sasa extract comprises tannin and the content thereof ranges from about 5 to 15% by mass on the basis of the solid content of the extract.
  • composition for use in treating and/or preventing periodontal disease according to the present invention comprises tannin originated from the Sasa plant in an amount preferably ranging from 0.05 to 7.5% by mass and more preferably 0.1 to 6% by mass as expressed in terms of the solid content thereof.
  • composition for use in treating and/or preventing periodontal disease according to the present invention comprises the Sasa extract as an effective component, but the antimicrobial activity thereof is further improved by the use of an appropriate amount of an organic acid in combination with the Sasa extract.
  • organic acids are malic acid, citric acid, lactic acid, oxalic acid, malonic acid, succinic acid, fumaric acid, acetic acid, benzoic acid, phenylacetic acid, salicylic acid and phenols.
  • malic acid particularly preferably used herein is malic acid.
  • the amount of the organic acid to be used preferably ranges from 0.01 to 5% by mass, more preferably 0.02 to 3% by mass and most preferably 0.05 to 1.5% by mass on the basis of the total mass of the composition for use in treating and/or preventing periodontal disease.
  • composition for use in the treatment and/or prevention of the periodontal disease comprises the combination of the Sasa extract and an organic acid, or the resulting composition may be further admixed with other components and/or a carrier.
  • dosage forms of the composition for use in the treatment and/or prevention of the periodontal disease may be liquid, solid or gaseous ones.
  • the composition for use in the treatment and/or prevention of the periodontal disease may be administered through either the oral route or any parenteral route.
  • Examples of the dosage forms of the composition are a tablet, a pill, a powdery preparation, a liquid preparation, a chewing gum, or various forms of foods such as a candy or starch jelly, a chocolate, bread, a cookie, buckwheat vermicelli and wheat vermicelli for the oral administration; and a tooth paste, a mouth wash, and dosage forms for the local administration (such as a cream and an ointment), for the parenteral administration.
  • Examples of such dosage forms for the local administration are those obtained by impregnating a carrier such as gauze made of natural or synthetic fibers with the composition for use in the prevention and/or treatment of the periodontal disease according to the present invention.
  • those for the local administration such as a cream and an ointment are preferably used since they are suitable for the direct application to an affected part suffering from the periodontal disease or a decayed tooth.
  • a base component such as an oily component, a humectant and/or an antiseptic, which are commonly used in pharmaceutical compositions, cosmetic products, compositions applied to the skin and compositions intra-orally administered (such as a tooth paste and a mouth wash).
  • Water used in the composition for use in the prevention and/or treatment of the periodontal disease are not restricted to particular ones and examples thereof include tap water, natural water and purified water, but preferably used herein is highly purified water such as ion-exchange water.
  • oils derived from animals such as squalane, tallow, lard, horse fat, lanolin and beeswax
  • oils derived from vegetables such as olive oil, grape seed oil, palm oil, jojoba oil and germ oil (such as rice germ oil)
  • synthetic or semi-synthetic oils such as liquid paraffin, higher fatty acid esters (such as octyl palmitate, isopropyl palmitate and octyl dodecyl myristate) and silicone oil.
  • the oily components are used in appropriate combinations while taking into consideration the performance requirement, for instance, an ability of protecting the skin, an effect of imparting emollient (or an effect of preventing drying of the skin and imparting softness and resilience to the skin through the coverage of the skin surface with a thin film) and an ability of imparting refreshed feeling to the skin.
  • the oily component comprises squalane, olive oil and octyl dodecyl myristate.
  • composition for use in the treatment and/or prevention of the periodontal disease comprises a solid oil component such as stearic acid, stearyl alcohol, behenic acid, cetanol and vaseline to control the hardness and flowability of the resulting composition and the composition preferably comprises stearic acid and cetanol in combination.
  • a solid oil component such as stearic acid, stearyl alcohol, behenic acid, cetanol and vaseline to control the hardness and flowability of the resulting composition and the composition preferably comprises stearic acid and cetanol in combination.
  • a creaming agent is used to convert the mixture of the Sasa extract, water and an oily component into a cream.
  • a creaming agent is not restricted to any particular one, but glycerin monostearate and a self-emulsifiable glycerin monostearate (a product obtained by incorporating an emulsifying agent into glycerin monostearate) are in general used in combination.
  • composition for use in the treatment and/or prevention of the periodontal disease according to the present invention may, if necessary, comprise other additives such as a stabilizer, a humectant (a wetting agent), a wound-healing agent, an antiseptic, a surfactant, a binder, a foaming agent, a sweetening agent, a refrigerant and/or an abrasive.
  • a stabilizer such as a humectant (a wetting agent), a wound-healing agent, an antiseptic, a surfactant, a binder, a foaming agent, a sweetening agent, a refrigerant and/or an abrasive.
  • stabilizers are a combination of a carboxy vinyl polymer with potassium hydroxide; polyethylene glycol distearate; and magnesium phosphate.
  • polyethylene glycol sesqui-stearate a 1:1 mixture of polyethylene glycol distearate and polyethylene glycol monostearate
  • the molecular weight of the polyethylene glycol ranging from 1000 to 20,000 is preferably used herein since it has high stability, is not separated into water and oil and the hardness required when the composition is applied to the skin in the form of a cream composition can effectively be controlled.
  • humectants usable herein are sodium salt of hyaluronic acid, collagen, an aloe extract (in particular, the aloe extract (2) derived from Aloe arborescens is preferred), urea, 1,3-butylene glycol, glycerin, trehalose, sorbitol, amino acids and sodium salt of pyrrolidone carboxylic acid.
  • wound-healing agents examples include allantoin, di-potassium glycyrrhizinate, a glycyrrhiza extract and a mugwort extract.
  • antiseptic is used subsidiarily since the Sasa extract has an antibiotic effect by nature.
  • antiseptics are sodium benzoate, lower alkyl esters of p-hydroxy benzoic acid (for instance, so-called paraben such as methyl, ethyl, propyl or butyl ester), sodium propionate, mixed fatty acid esters (a mixture of capric acid glyceryl, lauric acid glyceryl-2 and lauric acid polyglyceryl-10), phenoxy ethanol, light-sensitive substance No. 201 (yellow dye), and 1,2-pentanediol, with paraben, mixed fatty acid esters and 1,2-pentanediol being preferably used herein.
  • surfactants are sodium N-acyl-L-glutamate and polyoxyethylene sorbitan monostearate.
  • Examples of the binders usable herein include sodium carboxymethyl cellulose; examples of the foaming agents are sodium lauryl sulfate, sodium lauroyl glutamate, and sodium lauroyl sarcosinate; examples of the sweetening agents are xylitol, sorbitol and saccharin sodium; examples of the refrigerants include mint essence; and examples of the abrasives are calcium phosphate, calcium hydrogen phosphate and silica.
  • composition may, if required, comprise aroma components such as orange oil, lemon oil, bitter orange peel oil and perfumes.
  • Table 1 shows preferred amounts (% by mass) of the foregoing ingredients required for preparing the composition for use in the treatment and/or prevention of the periodontal disease in the form of a cream composition.
  • the amount of each component other than water is based on the total mass of the foregoing components other than water.
  • Table 1 Component Preferred range More preferred range Most preferred range Sasa extract 1 to 50 2 to 25 4 to 15 Liquid oily component 6 to 30 2 to 20 5 to 15 Solid oily component 2 to 35 3 to 25 5 to 15 Creaming agent 1 to 6 1.5 to 4 1.6 to 3 Stabilizer 0 to 2 0 to 1.5 0 to 1 Humectant 0 to 10 0.05 to 5 0.1 to 5 Wound-healing agent 0 to 2 0.05 to 1 0.1 to 0.5 Aroma component 0 to 5 0 to 3 0 to 1 Organic acid 0.01 to 5 0.1 to 3 0.5 to 1.5 Water Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance Balance
  • the foregoing components are introduced into a heating-mixing kettle equipped with a stirring blade and preferably an emulsifying apparatus and they are then admixed together at a temperature ranging from 70 to 90°C for 1 to 2 hours to thus form a composition for use in treating and/or preventing the periodontal disease according to the present invention.
  • composition for use in the treatment and/or prevention of the periodontal disease according to the present invention may be used in a variety of dosage forms such as an ointment, a liquid preparation, a jelly preparation, a gel-like preparation, an aerosol and other shapes, in addition to a cream composition, with a cream-like composition being preferably used herein because it can easily be used and show a considerably excellent effect.
  • the composition of the present invention may likewise be formed into a semi-solid or liquid product.
  • the composition for use in the treatment and/or prevention of the periodontal disease according to the present invention to the affected part such as the affected part of periodontal disease, the tooth root of a decayed tooth or the periodontium, in an appropriate amount on the order of, for instance, 0.1 to 1 g, at a frequency ranging from 1 to 5 times, usually 1 to 3 times a day, when it is used in the form of a cream composition.
  • the amount and frequency of application of the composition may appropriately be changed while taking into consideration, for instance, the symptoms of the disease.
  • composition for use in the treatment and/or prevention of the periodontal disease according to the present invention is desirably taken in an appropriate amount on the order of, for instance, 0.01 to 0.1 g/l kg of body weight at a frequency ranging from 1 to 5 times, usually 1 to 3 times a day, when it is administered through the parenteral route.
  • the amount and frequency of application of the composition may appropriately be changed while taking into consideration, for instance, the symptoms of the disease.
  • the Sasa extract used in the composition for use in the treatment and/or prevention of the periodontal disease according to the present invention as the effective component is an extract originated from a plant belonging to the genus Sasa Makino et Shibata and a 1.25% by mass aqueous solution thereof does not show any toxicity to the 293 cells derived from human fetal kidney.
  • composition for use in the treatment and/or prevention of the periodontal disease according to the present invention comprises the Sasa extract in an amount ranging from 1 to 50% by mass as expressed in terms of the solid content thereof and the composition thus shows significant antimicrobial activities against microorganisms such as periodontal disease-related microorganisms and bacteria belonging to Candida.
  • compositions for use in the treatment and/or prevention of the periodontal disease according to the present invention are as defined in the claims.
  • the moisture-containing solid contents thus treated were again introduced into a pressurized hot water-extraction tank and treated at 110°C for 5 minutes to thus obtain an extract.
  • the extracts obtained in the first and second extraction steps were combined together, filtered through a diatomaceous earth layer, the resulting filtrate was concentrated under reduced pressure till the solid content thereof was increased to 50% by mass and the concentrate thus prepared was subjected to a fluidized sterilization treatment at a temperature ranging from 110 to 130°C to give a Sasa extract.
  • the resulting Sasa extract was inspected for the sulfur content and it was found to be 3850 ⁇ m/ml (7.7 mg per one gram of the solid content).
  • the added amounts of a Sasa extract having a solid content of 8% by mass were 12.5, 25, 37.5 and 75% by mass in Examples 1 to 4, respectively (therefore, the contents of the extract as expressed in terms of the solid contents thereof were 1, 2, 3 and 6% by mass; and sulfur contents of these samples were 7.7 mg, 15.4 mg, 23.1 mg and 46.2 mg per 100 g of the composition for use in treating and/or preventing the periodontal disease, respectively).
  • Table 3 Component Amount (% by mass) Squalane 1.0 Olive oil 4.0 Orange oil 1.0 Octyl dodecyl myristate 6.0 Stearic acid 4.0 Cetanol 2.0 Polyethylene glycol distearate 0.5 Glycerin monostearate 1.0 Carboxy vinyl polymer (CARBOPOL 940) 0.2 Glycerin monostearate (self-emulsifiable type) 1.4 Sodium N-acyl-L-glutamate 0.2 1,3-Butylene glycol 1.0 Urea 3.0 Allantoin 0.1 Mixed fatty acid ester (NIKOGUARD DL) 0.5 Sasa extract (solid content: 8% by mass) 75.0 Potassium hydroxide 0.05 Ion-exchange water (Added to 100% by mass)
  • composition for use in treating and/or preventing the periodontal disease was found to have a sulfur content of 46.2 mg per 100 g of the composition.
  • the pH value of the resulting cream was found to be 6.00.
  • the pH value of the resulting cream was found to be 4.68.
  • Example 2 The same procedures used in Example 1 except that the amounts of the Sasa extract (solid content: 50% by mass) were set at 16%, 20% and 30% by mass and that the amount of purified water was adjusted in proportion thereto to thus give cream compositions for use in treating and/or preventing the periodontal disease according to the present invention, each having a content of the Sasa extract (solid content) of 8%, 10% or 15% by mass, respectively.
  • TWEBS a solution containing 50% by mass (as expressed in terms of the solid content) of the Sasa extract and 1% by mass of malic acid and having a pH value of about 5.0) available from HOUOUDOU CO., LTD. Sterilized distilled water was used as a diluent.
  • the test solution was in order diluted twofold to concentrations of 4, 2, 1 and 0.5%, while the concentration thereof was variously changed to 8, 7, 6, 5, 4, 3, 2 and 1% for the fungi belonging to Candida spp. to thus determine each corresponding minimum inhibitory concentration (MIC).
  • the minimum inhibitory concentration (MIC) was determined according to the agar plate-dilution technique using a GAM agar culture medium as the sensitivity-determining medium. The judgment was carried out after the cultivation under aerobic conditions over 24 hours for the facultative bacteria and after the cultivation under anaerobic conditions over 48 hours for the anaerobic bacteria. Each bacterium was inoculated at a bacterial density of about 10 6 cells per spot. A 2N NaOH aqueous solution or a 10% hydrogen chloride aqueous solution was, if desired, used to control the pH value of the culture medium.
  • a fungus belonging to Candida spp. was cultivated on a Mycocell-agar culture medium (BD) over 48 hours to thus obtain a colony of each strain to be tested (test strain), the colony was dispersed in an MH broth (available from Difco) to obtain a bacterial cell dispersion having a turbidity of McFarland#1, and then one platinum loop (10 ⁇ l) each of the resulting bacterial cell dispersion was inoculated into a series of sample solution-containing plate culture mediums according to the streaking-smearing technique. In this respect, one platinum loop of the resulting bacterial cell dispersion included about 10 6 bacterial cells. After cultivating each plate culture medium at 35°C for 24 hours, the culture mediums were visually observed for the confirmation of whether the bacterial cells underwent proliferation or not. The case wherein the bacterial cells underwent proliferation was judged to be (+).
  • Escherichia coli ATCC 25922 and Staphylococcus aureus ATCC 25923 were used as the strains for the management of the MIC precision.
  • Streptococcus mutans GTC 218 As an example of the decayed tooth-related bacteria.
  • control bacteria 5 strains of gram-positive cocci including Streptococcus pyogenes ATCC 19615 and Streptococcus pneumoniae ATCC 6305. These bacteria are pathogenic bacteria causing diseases of upper respiratory tracts such as the oral cavity and the pharyngeal cavity and it has been recognized that they do not belong to such decayed tooth-related bacteria. Pure-cultured bacteria aerobically cultivated on a blood-agar culture medium were used in the experiments.
  • Periodontal disease-related microorganisms Porphyromonas gingivalis ATCC 33277, Prevotella intermedia ATCC 25611, Bacteroides forthythus, Fusobacterium nucleatum ATCC 25586, Actinobacillus actinomycetemcomitans, and Capnocytophaga ohracea GAI-5586. These bacteria were subjected to the pure-cultivation on a Brucella HK blood-agar culture medium and the resulting pure-cultivated bacteria were used. In the cultivation, there were used anaerobic glove-boxes.
  • Candida albicans There were used 13 strains of Candida albicans and Candida glabrata in all. These strains were isolated from various kinds of clinical materials and stored in the anaerobic bacteria-experimental facilities affiliated with the medical department of Gifu University
  • Table 9 Antimicrobial Activities Against Decayed Tooth-Related Bacteria and Other Non-Related Cocci (10 6 ⁇ ml) Designation of Bacteria MIC of Sasa Ext. Test Sample Soln. Streptococcus mutans 2.0 Streptococcus pyogenes 2.0 Streptococcus pneumoniae 0.5 Streptococcus milleri group 2.0 Staphylococcus aureus 4 Enterococcus faecalis > 4 Table 10: Antimicrobial Activities against Periodontal Disease-Related Bacteria (10 7 ⁇ ml) Designation of Bacteria MIC of Sasa Ext. Test Sample Soln.
  • the Sasa extract of the present invention inhibited the growth of S. mutans at a concentration of 2% under acidic conditions (at a pH value ranging from 6.0 to 5.0).
  • the Sasa extract likewise inhibited the growth of the 4 kinds of periodontal disease-related bacteria examined above at a concentration of 2% under the same growth conditions.
  • the Sasa extract inhibited the growth of the fungi belonging to Candida spp. at a concentration of 5%.
  • Test Example 2 Ability of Sub-MIC Concentration of TWEBS to Reduce Amount of Extracellular Secretion of Porphyromonas gingivalis (Pg bacterium)
  • the term "dental plaque” herein used means the bio-film formed on a tooth.
  • This bio-film is constituted by a colony or mass of a plurality of bacteria living in and buried in the polymers originated from the bacteria and/or those originated from the saliva (Eps: Extracellular polysaccharide substances or glycocalyx).
  • the bio-film formed on the surface of a tooth is characterized in that it is quite hardly peeled off unlike those formed on the surface of the oral mucosa and that of the mucosa of tongue and further it would hardly be affected by a variety of antibacterial substances. Accordingly, it has been recognized that the dental plaque is quite important as a cause of the periodontal disease. It is important to destroy the same for the treatment of the periodontal disease and therefore, various studies have been conducted.
  • Pg bacterium is one of the most important anaerobic bacteria relating to the periodontal disease and it has been known that the bacterium can produce a powerful protease and that it plays an important role in the destruction of the gingiva.
  • the Pg bacteria extracellularly produce glycocalyx.
  • the protease produced by the Pg bacteria is extracellularly released by vesicles.
  • TWEBS has an extremely high antimicrobial activity against the Pg bacteria and that it can inhibit the growth of the bacteria at a concentration of 0.5%.
  • TWEBS was investigated for the effect thereof on the glycocalyx-producing ability of the Pg bacteria.
  • TWEBS inhibits the proliferation of Pg bacteria at such a lower concentration on the order of not more than 0.5% (MIC: 0.5%)
  • results obtained in Test Example 2 clearly indicate that TWEBS prevents the production or release of an extracellular substance originated from the Pg bacteria, which may be considered as glycocalyx, at the so-called sub-MIC concentration (0.2%) lower than the MIC.
  • composition of the present invention is useful as a composition for use in treating and/or preventing periodontal disease such as "periodontosis” which is assumed to be related to the abnormal proliferation of periodontal disease-related microorganisms within periodontal pockets and "decayed tooth” in which Streptococcus mutans is closely involved.
  • periodontal disease such as "periodontosis” which is assumed to be related to the abnormal proliferation of periodontal disease-related microorganisms within periodontal pockets and "decayed tooth” in which Streptococcus mutans is closely involved.

Landscapes

  • Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Animal Behavior & Ethology (AREA)
  • Epidemiology (AREA)
  • Natural Medicines & Medicinal Plants (AREA)
  • Engineering & Computer Science (AREA)
  • Chemical & Material Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Medicinal Chemistry (AREA)
  • Birds (AREA)
  • Mycology (AREA)
  • Microbiology (AREA)
  • Botany (AREA)
  • Biotechnology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Organic Chemistry (AREA)
  • Emergency Medicine (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medical Informatics (AREA)
  • Alternative & Traditional Medicine (AREA)
  • Oral & Maxillofacial Surgery (AREA)
  • Communicable Diseases (AREA)
  • Oil, Petroleum & Natural Gas (AREA)
  • Oncology (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Cosmetics (AREA)
  • Medicines Containing Plant Substances (AREA)
  • Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
  • Medicinal Preparation (AREA)

Claims (4)

  1. Zusammensetzung zur Verwendung für die Behandlung und/oder Vorbeugung einer periodontaler Krankheit, umfassend einen Sasa-Extrakt und eine organische Säure ausgewählt aus der Gruppe, bestehend aus Äpfelsäure, Zitronensäure, Milchsäure, Oxalsäure, Malonsäure, Succinsäure, Fumarsäure, Essigsäure, Benzoesäure, Phenylessigsäure, Salicylsäure und Phenolen, wobei der Sasa-Extrakt in einer Konzentration, ausgedrückt in Bezug auf den Feststoffanteil, im Bereich von 1 bis 50 Gew.-%, bezogen auf das Gesamtgewicht der Zusammensetzung, verwendet wird.
  2. Zusammensetzung zur Verwendung für die Behandlung und/oder Vorbeugung einer periodontaler Krankheit nach Anspruch 1, wobei die organische Säure Äpfelsäure ist.
  3. Zusammensetzung zur Verwendung für die Behandlung und/oder Vorbeugung einer periodontaler Krankheit nach Anspruch 1 oder 2, wobei sie in Form einer Creme vorliegt.
  4. Zusammensetzung zur Verwendung für die Behandlung und/oder Vorbeugung einer periodontaler Krankheit nach Anspruch 1 oder 2 oder 3, wobei die Menge an organischer Säure im Bereich von 0,01 bis 5 Gew.-%, bezogen auf das Gesamtgewicht der Zusammensetzung, liegt.
EP04771237A 2003-07-29 2004-07-29 Therapeutische und/oder präventive zusammsentzung für periodontale erkrankungen Expired - Fee Related EP1649864B1 (de)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
JP2003203199 2003-07-29
PCT/JP2004/011210 WO2005009454A1 (ja) 2003-07-29 2004-07-29 歯周病治療用及び／又は予防用組成物

Publications (3)

Publication Number Publication Date
EP1649864A1 EP1649864A1 (de) 2006-04-26
EP1649864A4 EP1649864A4 (de) 2007-11-14
EP1649864B1 true EP1649864B1 (de) 2010-09-29

Family

ID=34100625

Family Applications (1)

Application Number Title Priority Date Filing Date
EP04771237A Expired - Fee Related EP1649864B1 (de) 2003-07-29 2004-07-29 Therapeutische und/oder präventive zusammsentzung für periodontale erkrankungen

Country Status (8)

Country Link
US (3) US20060127330A1 (de)
EP (1) EP1649864B1 (de)
JP (1) JP4731323B2 (de)
KR (2) KR100884362B1 (de)
CN (1) CN1832751B (de)
DE (1) DE602004029367D1 (de)
HK (1) HK1092061A1 (de)
WO (1) WO2005009454A1 (de)

Families Citing this family (25)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2003105878A1 (ja) * 2002-01-20 2003-12-24 株式会社鳳凰堂 抗菌剤及び抗菌性組成物
US20050142233A1 (en) 2002-03-27 2005-06-30 Hououdou Co., Ltd. Compositions for treating and/or preventing pollinosis
JP4731323B2 (ja) * 2003-07-29 2011-07-20 株式会社鳳凰堂 歯周病治療用及び／又は予防用組成物
KR101159699B1 (ko) * 2006-03-10 2012-06-26 유조 츠치다 항미생물제 및 항미생물성 조성물
JP2009274957A (ja) * 2006-08-28 2009-11-26 Univ Nihon ベニカミキリフラスを有効成分とする歯周病原菌殺菌薬
KR100838270B1 (ko) * 2006-09-04 2008-06-17 우석대학교 산학협력단 구강세정제 조성물 및 그의 제조방법
JP5511183B2 (ja) * 2007-12-28 2014-06-04 アース製薬株式会社 有機酸による歯のエナメル質の溶解が阻害される口腔用組成物
US11951139B2 (en) 2015-11-30 2024-04-09 Seed Health, Inc. Method and system for reducing the likelihood of osteoporosis
US11844720B2 (en) 2011-02-04 2023-12-19 Seed Health, Inc. Method and system to reduce the likelihood of dental caries and halitosis
US20170100328A1 (en) * 2011-02-04 2017-04-13 Joseph E. Kovarik Bioadhesive Strip and Method of Using Same
US11998479B2 (en) 2011-02-04 2024-06-04 Seed Health, Inc. Method and system for addressing adverse effects on the oral microbiome and restoring gingival health caused by sodium lauryl sulphate exposure
US11951140B2 (en) 2011-02-04 2024-04-09 Seed Health, Inc. Modulation of an individual's gut microbiome to address osteoporosis and bone disease
KR101989765B1 (ko) * 2011-09-28 2019-06-14 라이온 가부시키가이샤 구강용 조성물
JP6425648B2 (ja) * 2013-03-27 2018-11-21 ライオン株式会社 口腔用組成物
US11833177B2 (en) 2013-12-20 2023-12-05 Seed Health, Inc. Probiotic to enhance an individual's skin microbiome
US11839632B2 (en) 2013-12-20 2023-12-12 Seed Health, Inc. Topical application of CRISPR-modified bacteria to treat acne vulgaris
US11826388B2 (en) 2013-12-20 2023-11-28 Seed Health, Inc. Topical application of Lactobacillus crispatus to ameliorate barrier damage and inflammation
US12005085B2 (en) 2013-12-20 2024-06-11 Seed Health, Inc. Probiotic method and composition for maintaining a healthy vaginal microbiome
US11969445B2 (en) 2013-12-20 2024-04-30 Seed Health, Inc. Probiotic composition and method for controlling excess weight, obesity, NAFLD and NASH
US11998574B2 (en) 2013-12-20 2024-06-04 Seed Health, Inc. Method and system for modulating an individual's skin microbiome
US11980643B2 (en) 2013-12-20 2024-05-14 Seed Health, Inc. Method and system to modify an individual's gut-brain axis to provide neurocognitive protection
RU2673473C2 (ru) * 2013-12-27 2018-11-27 Колгейт-Палмолив Компани Пребиотические композиции для ухода за полостью рта, содержащие карбоновые кислоты
JP6756553B2 (ja) * 2016-09-09 2020-09-16 株式会社 アルマード ジェル状歯磨き剤
JP6914654B2 (ja) * 2016-12-28 2021-08-04 ライオン株式会社 口腔用組成物
JP2020002019A (ja) * 2018-06-25 2020-01-09 ロート製薬株式会社 口腔用組成物

Family Cites Families (19)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3124506A (en) * 1964-03-10 Compositions containing lactic acid
JPS5446815A (en) * 1978-06-06 1979-04-13 Hoshi Pharma Production of pharmaceutical substance from leaves of *kumasasa*
JPS5785319A (en) * 1980-11-16 1982-05-28 Tsurui Yakuhin Kogyo Kk Agent for dental caries
JPS601018B2 (ja) * 1980-11-18 1985-01-11 昭和薬品化工株式会社 歯垢除去ならびに歯肉マツサージ用具
US5100652A (en) * 1984-03-21 1992-03-31 Alcide Corporation Disinfecting oral hygiene compositions and process for using the same
US4886657A (en) * 1984-07-30 1989-12-12 Ratcliff Perry A Method for preventing periodontitis
JPH01226806A (ja) 1988-03-04 1989-09-11 Chikusen Sangyo Kk 竹皮を添加物とする化粧品の製法
JPH08175946A (ja) * 1994-12-26 1996-07-09 Kao Corp 口腔用組成物
JP3488325B2 (ja) * 1995-09-28 2004-01-19 株式会社大和生物研究所 笹茶及びその製造方法
JP3212278B2 (ja) 1998-01-08 2001-09-25 眞悟 菊地 植物類、キノコ類から工場的にエキス製品を製造する製法及び装置
US6187324B1 (en) * 1998-08-11 2001-02-13 Kabushiki Kaisha Ogi Kogei Cosmetic composition comprising at least one of Kumazasa extract and medicinal carbon
AU4316200A (en) 1999-05-06 2000-11-21 Yuzo Tsuchida Cleansers containing LTiGTkumazasaLT/iGT extract
JP2001151655A (ja) * 1999-11-24 2001-06-05 Fine Kk 歯磨き
DE60130466T2 (de) * 2000-07-26 2008-06-12 Hououdou Co. Ltd. Antipruritische zusammensetzungen und die wundheilung fördernde zusammensetzungen
WO2003105878A1 (ja) * 2002-01-20 2003-12-24 株式会社鳳凰堂 抗菌剤及び抗菌性組成物
US20050142233A1 (en) 2002-03-27 2005-06-30 Hououdou Co., Ltd. Compositions for treating and/or preventing pollinosis
CN100400080C (zh) 2002-03-27 2008-07-09 株式会社凤凰堂 治疗和/或预防花粉症用的组合物
WO2004091640A1 (ja) 2003-04-11 2004-10-28 Hououdou Co.,Ltd. 皮膚保護組成物
JP4731323B2 (ja) * 2003-07-29 2011-07-20 株式会社鳳凰堂 歯周病治療用及び／又は予防用組成物

Also Published As

Publication number Publication date
HK1092061A1 (en) 2007-02-02
EP1649864A4 (de) 2007-11-14
EP1649864A1 (de) 2006-04-26
US20060127330A1 (en) 2006-06-15
KR100828656B1 (ko) 2008-05-09
CN1832751B (zh) 2010-05-26
WO2005009454A1 (ja) 2005-02-03
DE602004029367D1 (de) 2010-11-11
KR20060038955A (ko) 2006-05-04
US8343556B2 (en) 2013-01-01
US20080014292A1 (en) 2008-01-17
KR20080033546A (ko) 2008-04-16
CN1832751A (zh) 2006-09-13
JP4731323B2 (ja) 2011-07-20
US20130101529A1 (en) 2013-04-25
JPWO2005009454A1 (ja) 2006-10-19
KR100884362B1 (ko) 2009-02-18

Similar Documents

Publication Publication Date Title
US8343556B2 (en) Composition for treating and/or preventing periodontal disease
JP3159509B2 (ja) プロテアーゼ阻害剤
JP3969272B2 (ja) 抗う蝕、抗歯周病用組成物
KR20090088894A (ko) 쪽풀 추출물 분말과 그 제조 방법 및 그 쪽풀 추출물 분말의 용도
JPWO2004026273A1 (ja) 口腔用組成物
JP2848688B2 (ja) 口腔用組成物
JP3009531B2 (ja) 歯周病予防剤
KR20110088978A (ko) 생약 추출물을 함유하는 구강용 조성물
KR20030089047A (ko) 구강위생 증진용 조성물
EP1716859B1 (de) Pflanzenextrakte gegen Halitosis, Gingivitis oder Parodontitis
KR20160084904A (ko) 천연 약재 추출물을 유효 성분으로 함유하는 구강 위생 증진용 조성물
KR20170094609A (ko) 치주염 예방액의 제조 방법
JP4515732B2 (ja) グルコシルトランスフェラーゼ阻害剤、プラーク形成抑制剤、抗菌剤、口腔用剤およびう触予防用飲食物
KR20170103482A (ko) 연전초 추출물을 포함하는 구강질환 예방 또는 치료용 조성물
KR102580941B1 (ko) 쿼세틴 3-글루코시드를 포함하는 구강질환 예방 또는 치료용 조성물
KR20170134123A (ko) 에스트라갈로사이드를 포함하는 구강질환 예방 또는 치료용 조성물
KR20000038940A (ko) 나이신과 유지피 추출물을 함유한 구강위생증진용 조성물
KR20170103494A (ko) 과체 추출물을 포함하는 구강질환 예방 또는 치료용 조성물
KR20200002671A (ko) 청나래고사리 추출물을 포함하는 구강질환 예방 또는 치료용 조성물
KR20030080470A (ko) 충치와 치은염 예방 및 완화용 검 조성물
JP2004002268A (ja) コラゲナーゼ阻害剤及びその利用
KR20200114023A (ko) 마전자 추출물을 포함하는 구강용 조성물
KR20200135598A (ko) 손발톱 무좀 예방 및 개선제
KR20170142975A (ko) 익모초 추출물을 포함하는 구강질환 예방 또는 치료용 조성물
KR20170120404A (ko) 2-메톡시신남알데하이드를 포함하는 구강질환 예방 또는 치료용 조성물

Legal Events

Date Code Title Description
PUAI Public reference made under article 153(3) epc to a published international application that has entered the european phase

Free format text: ORIGINAL CODE: 0009012

17P Request for examination filed

Effective date: 20060126

AK Designated contracting states

Kind code of ref document: A1

Designated state(s): DE FR GB IT

DAX Request for extension of the european patent (deleted)
RBV Designated contracting states (corrected)

Designated state(s): DE FR GB IT

A4 Supplementary search report drawn up and despatched

Effective date: 20071016

RIC1 Information provided on ipc code assigned before grant

Ipc: A61K 9/06 20060101AFI20071009BHEP

Ipc: A61K 47/12 20060101ALI20071009BHEP

Ipc: A61P 1/02 20060101ALI20071009BHEP

Ipc: A61P 31/10 20060101ALI20071009BHEP

Ipc: A61P 31/04 20060101ALI20071009BHEP

17Q First examination report despatched

Effective date: 20080304

GRAP Despatch of communication of intention to grant a patent

Free format text: ORIGINAL CODE: EPIDOSNIGR1

GRAS Grant fee paid

Free format text: ORIGINAL CODE: EPIDOSNIGR3

GRAA (expected) grant

Free format text: ORIGINAL CODE: 0009210

AK Designated contracting states

Kind code of ref document: B1

Designated state(s): DE FR GB IT

REG Reference to a national code

Ref country code: GB

Ref legal event code: FG4D

REF Corresponds to:

Ref document number: 602004029367

Country of ref document: DE

Date of ref document: 20101111

Kind code of ref document: P

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: IT

Free format text: LAPSE BECAUSE OF FAILURE TO SUBMIT A TRANSLATION OF THE DESCRIPTION OR TO PAY THE FEE WITHIN THE PRESCRIBED TIME-LIMIT

Effective date: 20100929

PLBE No opposition filed within time limit

Free format text: ORIGINAL CODE: 0009261

STAA Information on the status of an ep patent application or granted ep patent

Free format text: STATUS: NO OPPOSITION FILED WITHIN TIME LIMIT

26N No opposition filed

Effective date: 20110630

REG Reference to a national code

Ref country code: DE

Ref legal event code: R097

Ref document number: 602004029367

Country of ref document: DE

Effective date: 20110630

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: FR

Payment date: 20120625

Year of fee payment: 9

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: GB

Payment date: 20120725

Year of fee payment: 9

PGFP Annual fee paid to national office [announced via postgrant information from national office to epo]

Ref country code: DE

Payment date: 20120726

Year of fee payment: 9

GBPC Gb: european patent ceased through non-payment of renewal fee

Effective date: 20130729

REG Reference to a national code

Ref country code: DE

Ref legal event code: R119

Ref document number: 602004029367

Country of ref document: DE

Effective date: 20140201

REG Reference to a national code

Ref country code: FR

Ref legal event code: ST

Effective date: 20140331

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: GB

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20130729

Ref country code: DE

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20140201

PG25 Lapsed in a contracting state [announced via postgrant information from national office to epo]

Ref country code: FR

Free format text: LAPSE BECAUSE OF NON-PAYMENT OF DUE FEES

Effective date: 20130731